1. Field of the invention
This invention relates to the field of trace molecule identification wherein molecules that are found to have been tagged with a tracer radioactive atom or rare stable isotope are catalogued according to their molecular structure. Although limitations in scope are not intended, this invention has particular relevance to the fields of biomedicine and biochemistry.
2. Description of the Prior Art
During the last fifteen years widespread interest has developed in a new mass spectrometer technique that uses an MeV accelerator as one element of a double mass spectrometer. This technique has been described, for example, in U.S. Pat. No. 4,037,100 to K. H. Purser and in an article entitled "Accelerator Mass Spectrometry" by D. Elmore and F. M. Phillips in Science at volume 236, pages 543-550 (1987). This technique, known as Accelerator Mass Spectrometry (AMS), has demonstrated the capability of measuring isotopic ratios as low as 1:10.sup.15 for many rare and radioactive isotopes and is one of the most sensitive analytical techniques available today. The reasons AMS achieves up to six orders of magnitude improvement in isotopic ratio sensitivity compared to that which is achievable using conventional mass spectroscopy are: (1) molecular interferences can be eliminated by fragmentation; (2) there are substantial reductions in small angle scattering; (3) Energy/Charge ambiguities are no longer an issue because direct measurements of kinetic energy become possible.
The first attempt to integrate AMS with biological procedures started in 1988 when workers used AMS to explore the role that xenobiotics play in initiating mutations. This attempt is described in an article entitled "Accelerator Mass Spectrometry in Biological Dosimetry. Relation between low-level exposure and covalent binding of heterocyclic amine carcinogens to DNA" by K. W. Turtletaub, J. S. Felton, J. S. Gledhill, J. R. Vogel, J. R. Southern, M. W. Caffee, M. W. Finkel, D. E. Nelson, I. P. Proctor and J. C. Davis in Proc. Nat. Acad. Science USA at volume 87 page 5288 (1990). With radiocarbon (.sup.14 C) as a tracer, the above referenced workers used hosts, which included cell lines, rodents and primates, to detect the effects of toxins, mutagens, carcinogens and chemical therapeutics in living systems. The usefulness of .sup.14 C is that it can be incorporated into most organic molecules. Furthermore, the site of the introduced radiocarbon atom can be accurately specified by the production procedure and located within the molecule at sites that are not subject to exchange. Compared to the scintillation counting method, this application of AMS to biology has resulted in a 6 order-of-magnitude increase in tracer detection sensitivity.
While such measurements are extremely sensitive and allow many new types of measurement, they provide no structural information about the molecule where the .sup.14 C finally resides. No knowledge is available from such measurements whether the .sup.14 C label is attached to the same compound that was administered at the beginning of a test or whether the original chemical has been modified by some metabolic process.
The present invention describes an analysis method that overcomes the above shortcoming. The method provides structural information while still retaining the high sensitivity of AMS.